Open AccessOn the Mode of Action of the Immunosuppressive Sesquiterpene Ovalicin
Author(s) -
ZIMMERMANN Wolfgang A.,
HARTMANN Guido R.
Publication year - 1981
Publication title -
european journal of biochemistry
Language(s) - English
Resource type - Journals
eISSN - 1432-1033
pISSN - 0014-2956
DOI - 10.1111/j.1432-1033.1981.tb05497.x
Subject(s) - incubation , hela , thymidine , in vivo , nucleoside , uridine , chemistry , dna synthesis , biochemistry , incubation period , biology , nucleoside analogue , in vitro , microbiology and biotechnology , rna , genetics , gene
When the potent immunosuppressive sesquiterpene ovalicin is added to lymphocyte cultures one first observes a preferential inhibition of uridine incorporation into rRNA. The uptake of the nucleoside, its conversion into the triphosphate or the polymerizing activity itself are not affected A longer period of incubation with the drug results in a marked decrease in the number of ribosomes, with a concomitant reduction of the rate of leucine incorporation into all cellular proteins. After extended periods of time, the incorporation of thymidine into DNA in stimulated lymphocytes as well as in S 49.1 lymphoma cells is inhibited by 1 nM ovalicin or less, although part of the incorporation seems to be resistant to the drug even at much higher concentrations. A similar effect is observed with 3T6 mouse fibroblasts or HeLa cells. Here, however, a much longer incubation with the drug is required. This observation explains the selective effect of ovalicin on lymphocytes observed in vivo .